The molecular cloning of the lymphoid-restricted transcription factor, Oct-2, helped to define the POU-domain transcription factor multigene family. POU-domain transcription factors regulate gene expression in a variety of cell lineages during development. Oct-2 is expressed in B lymphocytes and is critical for the lymphoid-specific expression of immunoglobulin genes. Most non-B cells in adult bone marrow express very little Oct-2 but as lymphoid progenitor cells differentiate into pre-B cells, Oct-2 expression is up-regulated. A unique regulatory role for Oct-2 in the T cell lineage is suggested by its induction during T cell activation by cognate antigen. Another POU-domain transcription factor that has been cloned and studied in our laboratory, Oct-3, functions at the earliest stages of mammalian development. Oct-3 binds to the same DNA motif as Oct-2 yet has a distinct pattern of expression. Oct-3 is expressed in the pluripotent stem cells of early mammalian embryos and is then down-modulated when these cells become committed to more differentiated lineages. Oct-3 expression is, however, maintained in the germ cell lineage. The expression pattern places Oct-3 in marked contrast with all previously cloned transcription factors which are only detectable after stem cells have differentiated along one of the somatic lineages. We have shown that the Oct-3 mRNA present in oocytes is transferred to the one cell embryo and is absolutely required for embryonic DNA synthesis and cell division. Oct-3 is thus the first described mammalian maternal effect gene. Interestingly. little if any transcription takes place in one-cell embryos, raising the possibility that Oct-3 directly regulates chromosomal DNA replication.